Evaluation of Adequacy of Control of Chemotherapy Induced Vomiting in Paediatric Patients With

113 Pages·2017·1.88 MB·English

by  Manghe Zephaniah Kiambi

EVALUATION OF ADEQUACY OF CONTROL OF CHEMOTHERAPY INDUCED
VOMITING IN PAEDIATRIC PATIENTS WITH CANCER AT KENYATTA
NATIONAL HOSPITAL

MANGHE ZEPHANIAH KIAMBI
(U56/82680/2015)

A research dissertation submitted in partial fulfillment of the requirement for the award of
Master of Pharmacy in Clinical Pharmacy by the University of Nairobi.

October, 2017
DECLARATION OF ORIGINALITY
Name: Manghe Zephaniah Kiambi

Registration number: U56/82680/2015

College: College of Health Sciences

School: School of Pharmacy

Department: Pharmaceutics and pharmacy practice

Course name: Masters of Pharmacy (Clinical Pharmacy)

Title of the study: Evaluation of adequacy of contr ol of chemotherapy induced
vomiting in paediatric patients with cancer at KNH

1. I understand what plagiarism is and I am aware of the University’s policy in this
regard.
2. I declare that this dissertation is my original work and has not been submitted
elsewhere for examination, award of a degree or publication. Where other people’s
work or my own work has been used, this has properly been acknowledged and
referenced in accordance with the University of Nairobi’s requirements.
3. I have not sought or used the services of any professional agencies to produce this
work.
4. I have not allowed, and shall not allow anyone to copy my work with the intention of
passing it off as his/her own work.
5. I understand that any false claim in respect of this work shall result in disciplinary
action, in accordance with university’s plagiarism policy.

Signature: ............................................... Date: ......................................................

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Supervisors’ approval
This dissertation has been submitted for evaluation for research and examination with our
approval as university supervisors.

1. DR. PETER NDIRANGU KARIMI, M. Pharm., Msc.MBA
Department of Pharmaceutics and Pharmacy Practice, University of Nairobi

Signature__________________________ Date____________________________

2. DR. DAVID ETALE WATA, M. Pharm.
Clinical Pharmacist, Kenyatta National Hospital

Signature__________________________ Date____________________________
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ABSTRACT
Background
Chemotherapy-induced nausea and vomiting (CINV) is a common side effect associated with
various chemotherapy regimens. To mitigate this phenomenon, several classes of antiemetics
are recommended for use before and after chemotherapy administration. This includes agents
like serotonin type 3 receptor antagonists (5-HT RA’s), corticosteroids and neurokinin type 1
3
receptor antagonists (NK RA’s). There is scanty information on CINV prophylaxis and level
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of control of vomiting in children with cancer in Kenyatta National Hospital.

Objective
The main aim was to assess the adequacy of control of vomiting in paediatric patients with
cancer at Kenyatta National Hospital.

Methodology
A longitudinal study design was adopted. Universal sampling technique was used. Patients
who satisfied the inclusion criteria were followed up prospectively up to 120 hours post
chemotherapy to assess the incidence of vomiting. Complete response was used as the
primary endpoint in assessing adequacy of control of emesis in the acute, delayed and overall
follow up period. A structured questionnaire was used as the data collection and entry tool
during the study period. Data was then analyzed using STATA version 13.0 software.
Univariate analysis was done and presented as frequency tables. Bivariate analysis was done
using Fisher’s exact as a test of significance. Binary logistic regression was done to assess the
strengths of the association. The level of significance adopted in the analysis was 0.05.

Results
The study population age ranged from 5 to 12 years with a mean age of 8.4±2.3 years. There
was male predominance 58 (65.9%). Overall, 86 (97.7%) study participants got acute emesis
prophylaxis. In the acute vomiting phase 77 (87.5%) got ondansetron monotherapy as
prophylaxis, 6 (6.8%) got granisetron monotherapy while 3 (3.4%) got ondansetron and
dexamethasone combination. Two (2.3%) patients did not receive prophylaxis in the acute
phase. In the delayed emesis phase 10 (11.4%) study participants got prophylaxis. Out of
those, 3 (3.4%) got ondansetron and dexamethasone combination while 7 (8%) got
ondansetron monotherapy. Rescue treatment was given to 13 (14.77%) out of 58 (65.9%)
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patients who had at least one episode of emesis. Complete response in the acute, delayed and
overall follow up period was 47 (53.41%), 49 (55.7%) and 30 (34.09%) respectively. Peak
emesis was reported on the first day 41 (46.6%) and reduced gradually over the follow up
period. Duration of chemotherapy was found to increase the risk of delayed emesis (OR 4.91
95%CI (1.66 – 14.57), p=0.004). Chemotherapy regimen composition affected risk of emesis;
platinum based regimens increased the risk of emesis (OR 20.36 95%CI (1.52 – 272.98),
p=0.023) while presence of a steroid in the chemotherapy regimen decreased risk of vomiting
(OR 0.26 95%CI (0.09 – 0.75), p = 0.012). High emetogenic chemotherapy increased the risk
of emesis (OR 3.30 95%CI (1.22 – 8.88), p = 0.018) compared with moderately and low
emetogenic chemotherapy.

Conclusion
Management of acute and delayed emesis in children still remains a big challenge. There was
poor compliance with local and international guideline recommendations for management of
chemotherapy induced vomiting.

Recommendations
Further studies can should assess the reasons for poor adherence to current CINV
management guidelines and address the challenges and gaps in practice.

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DEDICATION
This dissertation is dedicated to children; especially those with cancer.

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ACKNOWLEDGEMENT
First and foremost, I thank God for His blessings and sustenance throughout the writing of
this dissertation. Much thanks and appreciation goes to my supervisors, Dr P. Karimi and Dr.
D. Wata, for their invaluable input during the writing of this dissertation. I thank all the study
participants and their caregivers, healthcare workers at the paediatric wards at KNH and
colleagues for their unwavering support. I thank the entire hospital administration for giving
me an opportunity and sponsorship to pursue my master’s degree. Much thanks and love goes
to my wife, children and the entire family who were very supportive during the writing of this
dissertation.

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Table of Contents
DECLARATION OF ORIGINALITY ............................................................................................... ii
ABSTRACT ..................................................................................................................................... iv
DEDICATION ................................................................................................................................. vi
ACKNOWLEDGEMENT ............................................................................................................... vii
LIST OF TABLES ........................................................................................................................... xi
LIST OF FIGURES ........................................................................................................................ xiii
ABBREVIATIONS AND ACRONYMS ........................................................................................ xiv
OPERATIONAL DEFINITION OF TERMS ................................................................................. xvii
CHAPTER ONE: INTRODUCTION ................................................................................................ 1
1.1 Background to the study........................................................................................................... 1
1.1.1 Pathophysiology of vomiting ............................................................................................. 1
1.1.2 Classification of CINV ...................................................................................................... 2
1.2 Problem Statement ................................................................................................................... 4
1.3 Purpose of the study ................................................................................................................. 4
1.4 Objectives ................................................................................................................................ 5
1.5 Research Questions .................................................................................................................. 5
1.6 Significance and anticipated output .......................................................................................... 5
1.7 Study limitations ...................................................................................................................... 6
1.8 Conceptual Framework ............................................................................................................ 6
CHAPTER TWO: LITERATURE REVIEW ..................................................................................... 8
2.1 Introduction ............................................................................................................................. 8
2.1.1 Risk factors for CINV ....................................................................................................... 8
2.2 Antiemetic therapies for CINV............................................................................................... 11
2.2.1 5-HT receptor antagonists .............................................................................................. 11
3
2.2.2 Neurokinin receptor antagonists ...................................................................................... 11
2.2.3 Corticosteroids ................................................................................................................ 12
2.2.4 Dopamine receptor antagonists ........................................................................................ 12
2.2.5 Benzodiazepines ............................................................................................................. 13
2.2.6 Cannabinoids .................................................................................................................. 13
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2.2.7 Antihistamines ................................................................................................................ 13
2.2.8 Herbal medicines/alternative therapies............................................................................. 14
2.2.9 Principles of emesis control as per current guidelines ...................................................... 14
2.3 Incidences of nausea and vomiting ......................................................................................... 19
2.3.1 CINV incidences in HEC ................................................................................................ 19
2.3.2 CINV incidences IN MEC ............................................................................................... 19
CHAPTER THREE: MATERIALS AND METHOD ...................................................................... 21
3.1 Research Design .................................................................................................................... 21
3.2 Location of the Study ............................................................................................................. 21
3.3 Target Population................................................................................................................... 21
3.4 Inclusion/Exclusion criteria .................................................................................................... 21
3.4.1 Inclusion criteria ............................................................................................................. 21
3.4.2 Exclusion criteria ............................................................................................................ 21
3.5 Sample size determination ..................................................................................................... 22
3.5.1 Sampling technique ............................................................................................................. 22
3.6 Research Instruments ............................................................................................................. 22
3.7 Pilot Study ............................................................................................................................. 23
3.8 Validity ................................................................................................................................. 23
3.9 Reliability .............................................................................................................................. 24
3.10 Data Collection Techniques ................................................................................................. 24
3.12 Data Analysis....................................................................................................................... 25
3.13 Ethical Considerations ......................................................................................................... 25
CHAPTER FOUR: RESULTS ........................................................................................................ 26
4.1 Patients recruitment process ................................................................................................... 26
4.2 Socio-demographic characteristics. ........................................................................................ 26
4.4: Antiemetic response rates ..................................................................................................... 33
4.5 Bivariate analysis ................................................................................................................... 36
4.6: Adherence to guideline recommendations ............................................................................. 41
4.7 Logistic regression analysis.................................................................................................... 43
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5.0 DISCUSSION ........................................................................................................................... 49
5.1 Conclusion............................................................................................................................. 52
6.0 References ................................................................................................................................. 53
7.0 Appendices ................................................................................................................................ 60
7.1 Appendix I: Questionnaire ..................................................................................................... 60
7.2 Appendix II: Consent and assent documents ........................................................................... 65
7.2.1 Consent information sheet (English version) .................................................................... 65
7.2.2 Consent information form (Swahili version) .................................................................... 69
7.2.3 Consent certificate (English version) ............................................................................... 73
7.2.4 Consent certificate (Swahili version) ............................................................................... 75
7.2.5 Assent information form (English version) .................................................................... 78
7.2.6 Assent information (Swahili version)............................................................................... 82
7.2.7 Assent certificate (English version) ................................................................................. 86
7.2.8 Assent certificate (Swahili version) ............................................................................... 89
7.3 Appendix III: Ethical approval and clearances ........................................................................ 92

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